The effect of interrupted Anti-Retroviral Treatment (ART) on the reconstitution of memory and naive T cells during tuberculosis treatment in HIV active pulmonary tuberculosis patients

Abstract

Human Immunodeficiency Virus type-1(HIV-1) and active pulmonary tuberculosis (TB) both perturbe the immune system and lead to progression of each other. Administration of antiretroviral therapy ART) combined with anti-tuberculosis therapy in co-infection restores protective immune responses against the two infections. This study aimed at describing the immune reconstitution of naive and memory T cell populations in individuals receiving ART and anti-TB treatment in HIV/ TB patients.

Participants were randomised to receive ART/anti-TB treatment (intervention arm n =39) or receive only tuberculosis treatment (control arm n =37). The CD45RO and CD62L cellular markers were used to differentiate naive from memory T cells on CD4+ and CD8+ T cells using a BD 4-color flow cytometer FACS Calibre. Plasma HIV-RNA copy levels were measured using Roche Amplicor quantitative restriction transcriptase polymerase chain reaction assay (PCR). Samples were analysed at baseline, 3, 6 and 12 months time points.

The ART concurrently administered with TB therapy caused significant increases in CD8+ naive T cells unlike TB treatment alone. When ART was interrupted, there was significant decrease in the naive CD8+ T cells but not CD4+ T cells. Overall, ART preserved CD4+ and CD8+ naive and memory T cell pool in the periphery. There were no significant changes in immune reconstitution of naive and memory CD4+ and CD8+ T cells under TB treatment alone arm. Concurrent ART and tuberculosis treatment gradually increased and preserved naive CD8+ and CD4+ T cells in adults HIV-1 co-infected with TB with CD4 cell counts >350 cells/mm3. For better reconstitution of CD4+ and CD8+ T cell populations both ART and tuberculosis treatment should administered to HIV patients co-infected with tuberculosis. Interrupting ART did not yield immune reconstitution and virological benefits.